UGT1A1 gene

The UGT1A1 gene belongs to a family of genes that provide instructions for making enzymes called UDP-glucuronosyltransferases. 

These enzymes perform glucuronidation, in which a compound called glucuronic acid is conjugated to one of a number of different substances.



UGT1A1 gene, produces the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme: it is the only enzyme that glucuronidates bilirubin, a substance produced when red blood cells are broken down. 



The bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme converts the toxic form of bilirubin, which is unconjugated bilirubin to its nontoxic form, conjugated bilirubin, making it able to be dissolved and removed from the body.



The bilirubin-UGT enzyme is primarily found in cells of the liver, where bilirubin glucuronidation takes place. 



Conjugated bilirubin is dissolved in bile and excreted with solid waste.



Jaundice is common in newborns, mutations in the UGT1A1 gene increase the risk of developing a more severe condition called transient familial neonatal hyperbilirubinemia. 



Familial neonatal hyperbilirubinemia is associated with severe unconjugated hyperbilirubinemia and jaundice occur in newborns and usually disappear in 1 to 2 weeks. 



With familial neonatal hyperbilirubinemia is associated with severe unconjugated hyperbilirubinemia and jaundice, some babies develop kernicterus, hearing loss, or other neurological problems. 



Familial neonatal hyperbilirubinemia can be fatal.



The G71R mutation is the most common mutation associated with transient familial neonatal hyperbilirubinemia. 



Asian individuals, not white, newborns with a UGT1A1 gene mutation seem to be at risk of developing this condition.



Unconjugated bilirubin levels increase when the baby is breastfed, causing jaundice, and return to normal when breastfeeding is stopped for a prolonged period: breast milk jaundice.



Breast milk jaundice appears 5 or 10 days after birth and disappears at around 4 months of age. 



Kernicterus is not typically seen in infants with breast milk jaundice. 



A substance in breast milk of mothers of affected infants blocks glucuronidation.



The G71R mutation, and the mutation is thought to underlie the unconjugated hyperbilirubinemia. 



UGT1A1 gene polymorphisms influence Irinotecan related toxicity, with Increased gastrointestinal toxicity.


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